Clinicopathological and prognostic significance of programmed cell death ligand1 (PD-L1) expression in patients with non-small cell lung cancer: a meta-analysis.

OBJECTIVE: Programmed cell death 1 (PD-1) and one of its ligands, PD-L1, are key immune checkpoint proteins. Evidences showed PD-L1 is an emerging biomarker for immunotherapy by anti-PD-1 and anti-PD-L1 antibody in non-small cell lung cancer (NSCLC). To investigate the association of PD-L1 protein expression with clinicopathological features and its impact on survival outcome, we conducted a meta-analysis. METHODS: A comprehensive literature search of electronic databases (up to July 10, 2014) was performed. Correlation between PD-L1 expression and clinicopathological features and overall survival (OS) was analyzed by synthesizing the qualified data. Publication biases were examined. RESULTS: A total of 1,550 NSCLC patients from 9 studies were included. The pooled odds ratios (ORs) indicated high PD-L1 expression was associated with poor tumor differentiation [OR =0.53, 95% confidence interval (CI): 0.39-0.72, P<0.0001]. Whereas, none of other clinicopathological characteristics [gender, smoking status, histological type, invasive depth of tumor, status of lymph node metastasis and tumor node metastasis (TNM) stage] were correlated with PD-L1 expression in current analysis. The combined hazard ratio (HR) for OS showed high expression of PD-L1 impaired the OS in NSCLC (HRpositive/negative =1.47, 95% CI: 1.19-1.83, P=0.0004). CONCLUSIONS: Our meta-analysis indicated PD-L1 protein expression in NSCLC was not associated with common clinicopathological characteristics, except tumor differentiation. It was a poor prognostic biomarker for NSCLC. Further research should be performed to investigate the precise clinicopathological and prognostic significance of PD-L1 in NSCLC under uniform testing standard.

S-1-based versus 5-FU-based chemotherapy as first-line treatment in advanced gastric cancer: a meta-analysis of randomized controlled trials.

To compare the efficacy, prognosis, and toxicity of S-1-based with fluorouracil (5-FU)-based chemotherapy in patients with advanced gastric cancer (AGC) as first-line treatment, we performed this meta-analysis of all eligible randomized controlled trials (RCTs). A comprehensive literature search of electronic databases (up to February 20, 2014) was performed. Additionally, abstracts presented at the American Society of Clinical Oncology (ASCO) conferences held between January 2000 and February 2014 were searched to identify relevant trials. Overall response rate (ORR), time to treatment failure (TTF), overall survival (OS), and grade 3 or 4 toxicities were analyzed. Six RCTs with 2,264 patients of AGC were included. Meta-analysis demonstrated that S-1-based therapy was associated with better OS compared with 5-FU-based therapy (hazard ratio (HR) = 0.80, 95 % confidence interval (CI) 0.80-0.99, P = 0.03). Pooled estimate has showed the trend of superiority of S-1-based therapy in the aspect of ORR (odds ratio (OR) = 1.55, 95 % CI 0.87-2.77, P = 0.14) and TTF (HR = 0.73, 95 % CI 0.53-1.00, P = 0.05), but the difference was not significant. The incidence of toxicities of 5-FU-based regimens was significantly higher for thrombocytopenia (OR = 0.60, 95 % CI 0.42-0.88, P = 0.008) and stomatitis (OR = 0.22, 0, 95 % CI 0.05-0.9, P = 0.03). Based on the published studies, S-1-based therapy was superior to 5-FU-based therapy in OS and safety profile as first-line treatment in AGC. It was prone to improving ORR and TTF, though the difference was not significant. More high-quality randomized controlled trials should be performed to provide more information in comparing these two regimens.

[Efficacy of gefitinib on advanced non-small cell lung cancer in expanded access program (EAP)].

BACKGROUND & OBJECTIVE: Gefitinib is a selective inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, and has been used in treating advanced non-small cell lung cancer (NSCLC). This study was to evaluate the efficacy of Gefitinib on advanced NSCLC, and observe adverse events. METHODS: An open labeled, expanded access program (EAP) was conducted. Pathologically confirmed advanced NSCLC patients who had progressed after systemic chemotherapy or was not suitable for systemic chemotherapy were eligible for this program. Gefitinib (250 mg) was orally administered daily till disease progression or intolerable adverse events developed. RESULTS: From Sep. 2002 to Mar. 2005, 120 patients were enrolled, and 103 of them were assessable for response. The objective response rate was 18.4% (19/103). The disease control rate was 51.5% (53/103). The median survival time was 6 months (0.5-33 months). Adverse events were generally mild (grade I or II), including skin rash (30.1%), dry skin (12.6%), and diarrhea (25.2%). Two (1.9%) patients developed grade III elevation of serum glutamate pyruvate transaminase (SGPT). No grade IV adverse event occurred. CONCLUSION: Gefitinib is effective in treating advanced NSCLC, and the adverse events are mild.

[Epidermal growth factor receptor mutation in Chinese patients with non-small cell lung cancer].

BACKGROUND & OBJECTIVE: Recent studies showed that somatic mutations in epidermal growth factor receptor (EGFR) tyrosine kinase (TK) domain are associated with sensitivity of non-small cell lung cancer(NSCLC) to TK inhibitor gefitinib. The mutations, including in-frame deletions at exon 19 and substitutions at exon 18 or exon 21, cluster around ATP-binding pocket of TK domain. The frequency of mutations are higher in Japanese patients than in American patients. This study was to analyze EGFR mutations in Chinese patients with NSCLC. METHODS: From Jun. to Oct. 2004, fresh specimens of lung cancer and corresponding normal lung tissue were collected from 52 consecutive NSCLC patients (39 men and 13 women) treated in Cancer Center of Sun Yat-sen University. All patients had not received treatment of gefitinib. DNA was extracted from the 52 specimens. Exons 19 and 21 were amplified by polymerase chain reaction (PCR), and sequenced and analyzed from both sense and antisense directions. RESULTS: Somatic mutations in TK domain of EGFR in tumors were identified from 10 of the 52 (19.2%) patients, including 7 cases of in-frame deletion in exon 19 and 3 cases of amino acid substitution in exon 21. Mutation rate was significantly higher in adenocarcinoma, adeno-squamous carcinoma, and bronchioloalveolar cancer than in squamous cell carcinoma [26.1% (6/23), 40.0% (2/5), and 50.0% (2/4) vs. 0 (0/20), P=0.025], and significantly higher in non-smokers than in smokers [41.8% (7/17) vs. 8.6% (3/35), P=0.009]. Mutation rate in women was similar to that in men [23.1% (3/13) vs. 18.0% (7/39), P=0.697]. CONCLUSION: EGFR mutation rate in Chinese NSCLC patients is similar to that in Japanese patients, and is obviously higher than that in Caucasian population.

[Gemcitabine plus cisplatin versus gemcitabine plus vinorelbine in treatment of advanced non-small cell lung cancer (NSCLC)].

BACKGROUND & OBJECTIVE: Although platin-based chemotherapy has become a standard treatment for non-small cell lung cancer (NSCLC), its severe toxicities limit clinical application, and a new replacement is required. The study was to evaluate the efficacy, survival rate and toxicity between the combination of gemcitabine and cisplatin (GP arm) and the combination of gemcitabine and vinorelbine (GN arm) in the treatment of advanced NSCLC. METHODS: Eighty-two patients with locally advanced or metastatic NSCLC were enrolled into this study. 42 patients and 40 patients were randomized into GP group and GN group respectively. The patients' characteristics were similar between the two groups. They were treated with gemcitabine (1 000 mg/m(2) d(1), d(8)) plus cisplatin (80 mg/m(2), d(1)) in GP group, or gemcitabine plus vinorelbine (25 mg/m(2) d(1), d(8)) in GN group. The chemotherapy was repeated every 3 weeks as a cycle. Every patient was treated two cycles at least. RESULTS: An objective response rate of 28.6% was observed in GP arm versus 25% in GN arm (P=0.346). The 1-year survival rate was 64% in GP arm and 66% in GN arm. The median survival time was 9.87 months for GN arm and 8.78 months for GP arm. Nausea and vomiting were the major dose-limiting toxicity. The incidence of grade III/IV nausea and vomiting was significantly higher in the GP arm than in the GN arm (P=0.000). The Leukopenia incidence was similar in two groups (P=0.130). CONCLUSION: The efficacy of GN regimen (platinum-free regimen) was similar to that of GP regimen, but the toxicity of GN regimen is lighter than that of GP regimen.